TY  - JOUR
A1  - Heinrich, Angela
A1  - Buchmann, Arlette F.
A1  - Zohsel, Katrin
A1  - Dukal, Helene
A1  - Frank, Josef
A1  - Treutlein, Jens
A1  - Nieratschker, Vanessa
A1  - Witt, Stephanie H.
A1  - Brandeis, Daniel
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
A1  - Rietschel, Marcella
T1  - Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence
JF  - Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man
N2  - Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur.
KW  - Epigenetic
KW  - Glucocorticoid receptor
KW  - Methylation
KW  - Externalizing disorders
KW  - Adolescents
Y1  - 2015
U6  - https://doi.org/10.1007/s10519-015-9721-y
SN  - 0001-8244
SN  - 1573-3297
VL  - 45
IS  - 5
SP  - 529
EP  - 536
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Buchmann, Arlette F.
A1  - Boecker-Schlier, Regina
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Wolf, Isabella
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume
JF  - Brain structure & function
N2  - Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.
KW  - FKBP5
KW  - Childhood adversity
KW  - Amygdala
KW  - fMRI
KW  - Connectivity
KW  - Voxel-based morphometry
Y1  - 2015
U6  - https://doi.org/10.1007/s00429-014-0729-5
SN  - 1863-2653
SN  - 1863-2661
VL  - 220
IS  - 3
SP  - 1355
EP  - 1368
PB  - Springer
CY  - Heidelberg
ER  -